SCN5A mutation identified in a patient with short-coupled variant of torsades de pointes.

Background Short-coupled variant of torsades de pointes (scTdP) is a disease characterized by TdP without QT prolongation, which is initiated by extremely short-coupled ventricular extra-systoles. Its genetic background remains rarely unveiled. Objective We aimed to identify genetic variations in patients with scTdP and to analyze the functional change of the mutant Na+ channel identified in a scTdP patient. Methods and results We performed genetic analysis for inherited arrhythmia-related 45 genes using next-generation sequencer (MiSeq, Illumina) among seven consecutive scTdP patients. We identified an SCN5A mutation R800H in a 38-year-old male who suffered ventricular fibrillation during dinner and was resuscitated. Two months later, he lost his consciousness at work. His Holter electrocardiogram showed scTdP. He had no family history of sudden cardiac death or heart disease. Functional analysis of the SCN5A-R800H channels showed a significantly shortened recovery time from inactivation. Peak sodium current densities in SCN5A-R800H were larger than those in wild type but the difference was not statistically significant. Conclusions We identified an SCN5A mutation in a scTdP patient and confirmed that the mutant channel caused the shortness of recovery time from inactivation. SCN5A might be a candidate gene for scTdP.